I plan to use leukemia L1210 cells and a subline L1210/PDD which has an experimentally developed resistance to the chemotherapeutic agent cisdiamminedichloroplatinum(II). The intention is to compare these two cell lines with respect to the uptake and binding of the drugs and the subsequent ability to stimulate DNA repair. (14C)-cis-dichloro(ethylenediammine)platinum(II), a drug to which L1210/PDD is similarly resistant will be synthesized and used as a sensitive monitor of these events. The combination of this radiolabeled drug with alkaline elution analysis and high pressure liquid chromatography will enable determination of the critical lesion(s) in the DNA and the capacity of the cell to repair it. The enzymes involved in repair of the lesions will be analyzed by their action on both purified L1210-modified DNA and in vitro modified PM2 bacteriophage DNA. A final aspect will be to analyze the stages in production of resistance with the aim of possibly reducing this problem during chemotherapy.